基于网络药理学研究海金沙治疗输尿管结石的作用机制

Study on the mechanism of Haijinsha in treating ureteral calculi based on network pharmacology

目的:从网络药理学的角度,研究中药海金沙治疗输尿管结石疾病的关键成分和作用机制。方法:通过中药系统药理数据库和分析平台(TCMSP),检索海金沙的有效成分和相关作用靶点,并利用Uniprot数据库匹配对应的基因名称;再通过GeneCards和Drugbank数据库查询获取输尿管结石疾病相关靶点,利用Cytoscape 3.9.1软件将海金沙-输尿管结石的交集靶点做网络可视化处理;通过String数据库构建相应的蛋白质-蛋白质相互作用关系图,再计算得出关键靶点基因;最后将相应的靶点基因数据通过Bioconductor数据库和R语言获得基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析各20条。结果:通过筛选,获得海金沙的有效成分共11种,海金沙与输尿管结石疾病相关的靶点共有15个,包括雄激素受体(Androgen Receptor,AR)、肾上腺素能受体α1β(Adrenoceptor Alpha 1B,ADRA1B)、前列腺素氧化环化酶2(Prostaglandin-Endoperoxide Synthase 2,PTGS2)、周期蛋白依赖激酶抑制因子1A(Cyclin Dependent Kinase Inhibitor 1A,CDKN1A)、肿瘤抑制蛋白p53(Tumor Protein p53,TP53)等;关键有效成分5个,包括金合欢素、香叶木素、常春藤皂苷元、β-谷甾醇、山柰酚。GO富集分析和KEGG富集分析确定各20条。GO分析包括生物过程、细胞组成和分子功能三部分。KEGG通路分析结果显示,海金沙治疗输尿管结石主要涉及卡波西肉瘤相关的疱疹病毒感染、化学致癌、脂质和动脉硬化等通路。结论:海金沙治疗输尿管结石是通过多成分、多靶点、多通路相互作用的结果,但是对于如何破坏结石成分或分解结石未有明确结论。

Objective:From the perspective of network pharmacology,to study the key components and mechanism of Haijinsha(Spora Lygodii)in treating ureteral calculi.Methods:The active ingredients and related action targets of Haijinsha were obtained by searching the TCMSP database,a systematic pharmacology database and analysis platform for TCM medicine,and the corresponding gene names were matched using the Uniprot database,then the targets related to ureteral stone disease were obtained by querying the GeneCards and Drugbank databases,and the Cytoscape 3.9.1 software was used to the network visualization was done by Cytoscape 3.9.1 software to visualize the intersecting targets of Haijinsha-ureteral calculi,the corresponding protein interactions were constructed by String database,and then the key target genes were calculated;finally,the corresponding target gene data were obtained by Bioconductor database and R language to obtain 20 GO and KEGG enrichment analysis each.Results:Through screening,there were 11 active ingredients of Haijinsha,and 15 targets of Haijinsha related to ureteral calculi,including AR,ADRA1B,PTGS2,CDKN1A,TP53,etc..A total of 5 key active ingredients,including acacetin,diosmetin,hederagenin,beta-sitosterol,kaempferol.GO enrichment analysis and KEGG enrichment analysis identified 20 each.The GO analysis included its biological process,cellular composition and molecular function.The results of KEGG pathway analysis showed that the main pathway of hesperidin for ureteral calculi involved Kaposi’s sarcoma-associated herpesvirus infection,chemical carcinogenesis,lipid and atherosclerosis.Conclusion:The treatment of ureteral calculi with Haijinsha is the result of a multi-component,multi-target and multi-pathway interaction,but there is no clear conclusion on how to destroy the stone components or break down the stones.